Mapping global brain reconfigurations following local targeted manipulations

Area of Science:

• Neuroscience
• Systems Neuroscience
• Computational Neuroscience

Background:

• Understanding localized brain interventions is key for neural function and therapy.
• Focal manipulations impact whole-brain dynamics, but mechanisms remain unclear.

Purpose of the Study:

• Investigate how focal brain interventions affect whole-brain dynamics.
• Elucidate the mechanisms driving global functional connectivity (FC) changes.
• Develop a framework for understanding region-specific FC reorganization.

Main Methods:

• Longitudinal functional MRI (fMRI) in mice.
• Focal interventions: thalamic lesions and chemogenetic silencing.
• Personalized mouse brain simulations incorporating experimental data.

Main Results:

• Local interventions disrupted sustained network-wide activity.
• Global FC reconfigurations were observed.
• Simulations showed local excitability alterations modulated distributed firing rates and frequency content, driving FC changes.
• Affected brain region topography was intervention-site-specific, acting as perturbation signatures.

Conclusions:

• Focal interventions induce consistent, region-specific global FC reorganization patterns.
• Provides mechanistic insights into systemic effects of localized neural modulation.
• Framework aids understanding of hypo-/hyperconnectivity observations and has potential for clinical diagnostics and personalized neuromodulation.